The scope and limitations of three independent, though related routes leading to 5-substituted tetrahydroisoquinolines are explored: the Pictet-Spengler type cyclization of ortho-substituted 2-phenylethylamines, the Pomeranz-Fritsch type cyclization of meta-substituted benzylamines and the electrophilic trapping of 5-lithiated 4-lithiooxytetrahydroquinolines. The introduction of the substituent relies in all three cases on a neighboring group assisted, site selective metalation step. [on SciFinder (R)]